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Target id: 1873

Nomenclature: OX40

Systematic Nomenclature: TNFRSF4

Family: Tumour necrosis factor (TNF) receptor family

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 1 277 1p36.33 TNFRSF4 TNF receptor superfamily member 4
Mouse 1 272 4 87.68 cM Tnfrsf4 tumor necrosis factor receptor superfamily, member 4
Rat 1 271 5q36 Tnfrsf4 TNF receptor superfamily member 4
Previous and Unofficial Names Click here for help
ACT35 | CD134 | TXGP1L | MRC OX40 | OX40L receptor | Tax-transcriptionally activated glycoprotein 1 | tumor necrosis factor (ligand) superfamily, member 4 | tumor necrosis factor receptor superfamily
Database Links Click here for help
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
RefSeq Nucleotide
RefSeq Protein
Natural/Endogenous Ligands Click here for help
OX-40 ligand {Sp: Human}
Adaptor proteins (Human)

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Key to terms and symbols Click column headers to sort
Antibody Sp. Action Value Parameter Reference
vonlerolizumab Peptide Primary target of this compound Hs Agonist - - 4
rocatinlimab Peptide Immunopharmacology Ligand Hs Inhibition - -
Antibody Comments
The anti-OX40 monoclonal antibodies (mAbs) GSK3174998, BMS-986178 [3] and MEDI6469 [2] are examples that are in active clinical development (as of Feb. 2021) as potential immuno-oncology agents [1]. Blocking OX40 signalling is predicted to enhance anti-tumour T cell immunity.
Other Binding Ligands
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
compound 1 [PMID: 24930776] Small molecule or natural product Immunopharmacology Ligand Hs Binding 5.9 pIC50 6
pIC50 5.9 (IC50 1.2x10-6 M) [6]
Immunopharmacology Comments
The OX40/OX40L axis is involved in late T cell costimulatory signalling and both partners are transiently expressed following antigen recognition. This checkpoint is particularly important for sustaining the effector function of Th1 and Th2 T cells. Blocking OX40/OX40L is reported to prevent the development of disease in in vivo autoimmune and inflammatory disease models [7]. Amgen and Kyowa Kirin are partnering on the latter's anti-OX40 antibody rocatinlimab (KHK4083/AMG451) with a focus on efficacy in atopic dermatitis [5], where Th2 effector cells are a driving factor.
Anti-OX40 mAbs are also being investigated for neoadjuvant activity, as a mechanism to enhance anti-tumour T cell activity in cancer patients [2].
Immuno Process Associations
Immuno Process:  Inflammation
Immuno Process:  T cell (activation)
Immuno Process:  B cell (activation)
Immuno Process:  Immune regulation
Immuno Process:  Cytokine production & signalling
Immuno Process:  Cellular signalling
Immuno Process:  Barrier integrity
Gene Expression and Pathophysiology Comments
Expression of OX40 is confined to activated effector T and effector memory T cells.


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1. Cebada J, Perez-Santos M, Bandala C, Lara-Padilla E, Herrera-Camacho I, Rosas-Murrieta NH, Millán-Pérez Peña L, Monjaraz E, Flores A, Anaya-Ruiz M. (2021) OX40 agonists for cancer treatment: a patent review. Expert Opin Ther Pat, 31 (1): 81-90. [PMID:32945223]

2. Duhen R, Ballesteros-Merino C, Frye AK, Tran E, Rajamanickam V, Chang SC, Koguchi Y, Bifulco CB, Bernard B, Leidner RS et al.. (2021) Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells. Nat Commun, 12 (1): 1047. [PMID:33594075]

3. Gutierrez M, Moreno V, Heinhuis KM, Olszanski AJ, Spreafico A, Ong M, Chu Q, Carvajal RD, Trigo J, De Olza MO et al.. (2021) OX40 Agonist BMS-986178 Alone or in Combination With Nivolumab and/or Ipilimumab in Patients With Advanced Solid Tumors. Clin Cancer Res, 27 (2): 460-472. [PMID:33148673]

4. Huseni M, Totpal K, Du C, Dalpozzo K, Zhu J, Rishipathak D, McNamara E, Jonshtone B, Hegde PS, Rhee I. (2014) Anti-tumor efficacy and biomarker evaluation of agonistic anti-OX40 antibodies in preclinical models. Journal for Immunotherapy of Cancer, 2 (Suppl 3): 105.

5. Nakagawa H, Iizuka H, Nemoto O, Shimabe M, Furukawa Y, Kikuta N, Ootaki K. (2020) Safety, tolerability and efficacy of repeated intravenous infusions of KHK4083, a fully human anti-OX40 monoclonal antibody, in Japanese patients with moderate to severe atopic dermatitis. J Dermatol Sci, 99 (2): 82-89. [PMID:32651105]

6. Song Y, Margolles-Clark E, Bayer A, Buchwald P. (2014) Small-molecule modulators of the OX40-OX40 ligand co-stimulatory protein-protein interaction. Br J Pharmacol, 171 (21): 4955-69. [PMID:24930776]

7. Webb GJ, Hirschfield GM, Lane PJ. (2016) OX40, OX40L and Autoimmunity: a Comprehensive Review. Clin Rev Allergy Immunol, 50 (3): 312-32. [PMID:26215166]


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